CZ294348B6 - Substituovaný derivát glycinu a farmaceutický prostředek s jeho obsahem - Google Patents
Substituovaný derivát glycinu a farmaceutický prostředek s jeho obsahem Download PDFInfo
- Publication number
- CZ294348B6 CZ294348B6 CZ19984042A CZ404298A CZ294348B6 CZ 294348 B6 CZ294348 B6 CZ 294348B6 CZ 19984042 A CZ19984042 A CZ 19984042A CZ 404298 A CZ404298 A CZ 404298A CZ 294348 B6 CZ294348 B6 CZ 294348B6
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- CZ
- Czechia
- Prior art keywords
- alkyl
- substituted
- ring
- group
- hydrogen
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- 150000002332 glycine derivatives Chemical class 0.000 title claims abstract description 68
- 239000008194 pharmaceutical composition Chemical class 0.000 title claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 144
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 128
- 239000001257 hydrogen Substances 0.000 claims abstract description 120
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 120
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 110
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 107
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 89
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 73
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 34
- 230000002265 prevention Effects 0.000 claims abstract description 22
- 208000008238 Muscle Spasticity Diseases 0.000 claims abstract description 17
- 208000018198 spasticity Diseases 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 206010015037 epilepsy Diseases 0.000 claims abstract description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 15
- 208000019022 Mood disease Diseases 0.000 claims abstract description 7
- 208000007101 Muscle Cramp Diseases 0.000 claims abstract description 7
- 150000001450 anions Chemical class 0.000 claims abstract description 7
- 150000001768 cations Chemical class 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 194
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 161
- -1 nitro, hydroxy Chemical group 0.000 claims description 155
- 125000001072 heteroaryl group Chemical group 0.000 claims description 76
- 125000003118 aryl group Chemical group 0.000 claims description 72
- 229910052760 oxygen Inorganic materials 0.000 claims description 70
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 65
- 239000001301 oxygen Substances 0.000 claims description 62
- 125000005842 heteroatom Chemical group 0.000 claims description 56
- 125000001424 substituent group Chemical group 0.000 claims description 52
- 229910052717 sulfur Inorganic materials 0.000 claims description 51
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 48
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 46
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 43
- 239000011593 sulfur Chemical group 0.000 claims description 43
- 238000006467 substitution reaction Methods 0.000 claims description 39
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 32
- 239000005977 Ethylene Substances 0.000 claims description 32
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 30
- 125000004423 acyloxy group Chemical group 0.000 claims description 30
- 125000004043 oxo group Chemical group O=* 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 29
- 125000006413 ring segment Chemical group 0.000 claims description 28
- 125000001153 fluoro group Chemical group F* 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 24
- 125000001589 carboacyl group Chemical group 0.000 claims description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 22
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 20
- 125000001246 bromo group Chemical group Br* 0.000 claims description 20
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 18
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 17
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 14
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 125000001118 alkylidene group Chemical group 0.000 claims description 14
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 14
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 13
- 208000002193 Pain Diseases 0.000 claims description 13
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- 208000006011 Stroke Diseases 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 230000001965 increasing effect Effects 0.000 claims description 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 11
- 201000000980 schizophrenia Diseases 0.000 claims description 11
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 10
- 239000000460 chlorine Chemical group 0.000 claims description 10
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 9
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 9
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 206010012289 Dementia Diseases 0.000 claims description 9
- 150000001721 carbon Chemical group 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 8
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 125000001931 aliphatic group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 230000030833 cell death Effects 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 8
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 6
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 241000534944 Thia Species 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 230000001737 promoting effect Effects 0.000 claims description 6
- 125000003003 spiro group Chemical group 0.000 claims description 6
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 5
- 206010019196 Head injury Diseases 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 5
- 201000003723 learning disability Diseases 0.000 claims description 5
- 230000016273 neuron death Effects 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- 210000003061 neural cell Anatomy 0.000 claims description 4
- 208000030507 AIDS Diseases 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 3
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- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 201000004810 Vascular dementia Diseases 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 208000010118 dystonia Diseases 0.000 claims description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000000815 N-oxide group Chemical group 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004450 alkenylene group Chemical group 0.000 claims description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000005872 benzooxazolyl group Chemical group 0.000 claims description 2
- 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 claims description 2
- 125000002720 diazolyl group Chemical group 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical group NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 238000005304 joining Methods 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004306 triazinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000006529 (C3-C6) alkyl group Chemical group 0.000 claims 1
- 241000209761 Avena Species 0.000 claims 1
- 235000007319 Avena orientalis Nutrition 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 208000005392 Spasm Diseases 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 126
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 82
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 235000019441 ethanol Nutrition 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 230000009467 reduction Effects 0.000 description 51
- 238000006722 reduction reaction Methods 0.000 description 51
- 238000000034 method Methods 0.000 description 47
- 239000000243 solution Substances 0.000 description 47
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 238000003786 synthesis reaction Methods 0.000 description 45
- 239000004471 Glycine Substances 0.000 description 44
- 229960002449 glycine Drugs 0.000 description 44
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 41
- 239000002904 solvent Substances 0.000 description 38
- 230000015572 biosynthetic process Effects 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- BTKSUULMJNNXHG-UHFFFAOYSA-N ethyl 2-(methylamino)acetate Chemical compound CCOC(=O)CNC BTKSUULMJNNXHG-UHFFFAOYSA-N 0.000 description 29
- 230000000694 effects Effects 0.000 description 28
- 238000002360 preparation method Methods 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- KTJRGPZVSKWRTJ-UHFFFAOYSA-N 3-chloro-1-phenylpropan-1-one Chemical compound ClCCC(=O)C1=CC=CC=C1 KTJRGPZVSKWRTJ-UHFFFAOYSA-N 0.000 description 22
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 20
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- CXQTTWVBUDFUNO-UHFFFAOYSA-N methyl piperidine-2-carboxylate Chemical compound COC(=O)C1CCCCN1 CXQTTWVBUDFUNO-UHFFFAOYSA-N 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 101710083171 Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 18
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- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 15
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
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- 230000027455 binding Effects 0.000 description 9
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- IFYCNKKHRHBRKA-UHFFFAOYSA-N ethyl 2-diethoxyphosphorylacetate;sodium Chemical compound [Na].CCOC(=O)CP(=O)(OCC)OCC IFYCNKKHRHBRKA-UHFFFAOYSA-N 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
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- SZIKRGHFZTYTIT-UHFFFAOYSA-N ethyl piperidine-2-carboxylate Chemical compound CCOC(=O)C1CCCCN1 SZIKRGHFZTYTIT-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 8
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- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 8
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- 229910010082 LiAlH Inorganic materials 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
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- 230000008733 trauma Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 0.000 description 1
- MDDPTCUZZASZIQ-UHFFFAOYSA-N tris[(2-methylpropan-2-yl)oxy]alumane Chemical compound [Al+3].CC(C)(C)[O-].CC(C)(C)[O-].CC(C)(C)[O-] MDDPTCUZZASZIQ-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
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Classifications
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- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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- C07D279/26—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom without other substituents attached to the ring system
-
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
- C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
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- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/64—Oxygen atoms
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
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- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
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- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
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- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C07—ORGANIC CHEMISTRY
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- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
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- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
- C07C2603/32—Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
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- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/86—Ring systems containing bridged rings containing four rings
- C07C2603/88—Ethanoanthracenes; Hydrogenated ethanoanthracenes
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- Chemical & Material Sciences (AREA)
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- Pyrrole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
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CZ19984042A CZ294348B6 (cs) | 1996-05-31 | 1997-05-29 | Substituovaný derivát glycinu a farmaceutický prostředek s jeho obsahem |
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SK16662000A3 (sk) * | 1998-03-26 | 2001-05-10 | University Of Saskatchewan Technologies Inc. | Alifatické aminokarboxylové a aminofosfónové kyseliny, aminonitrily a aminotetrazoly ako bunkové záchranné činidlá |
US6984754B1 (en) | 1998-03-26 | 2006-01-10 | University Of Saskatchewan Technologies Inc. | Aliphatic amino carboxylic and amino phosphonic acids amino nitriles and amino tetrazoles as cellular rescue agents |
IL139008A0 (en) * | 1998-04-14 | 2001-11-25 | Gen Hospital Corp | Methods for treating neuropsychiatric disorders |
TW555757B (en) * | 1998-07-31 | 2003-10-01 | Akzo Nobel Nv | Aminomethylcarboxylic acid derivatives |
DE19840611A1 (de) * | 1998-09-05 | 2000-03-09 | Klaus Wanner | GABA-uptake-Inhibitoren mit Pyrrolidinstruktur |
EP1196386A2 (en) * | 1999-07-06 | 2002-04-17 | Vertex Pharmaceuticals Incorporated | N-substituted glycine derivatives |
TWI243173B (en) | 1999-11-17 | 2005-11-11 | Akzo Nobel Nv | Spiro[2H-1-benzopyran-2,4'-piperidine] derivatives |
DOP2001000189A (es) | 2000-06-30 | 2002-03-30 | Pfizer Prod Inc | Benzofenonas y sulfonas como inhibidores de la captación de glicina |
US7049343B2 (en) | 2000-09-08 | 2006-05-23 | Merck & Co., Inc. | Substituted hydrazine derivatives |
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AR032653A1 (es) | 2001-02-09 | 2003-11-19 | Telik Inc | Inhibidores heterociclicos del trasportador de glicina 2 composiciones farmaceuticas, uso y metodos. |
MXPA03007309A (es) * | 2001-02-16 | 2004-06-30 | Allelix Neuroscience Inc | Derivados de amina sustituidos por tiofeno como inhibidores glyt-1. |
US6566550B2 (en) * | 2001-06-21 | 2003-05-20 | Pfizer Inc | Substituted aromatic ethers as inhibitors of glycine transport |
ATE305917T1 (de) * | 2001-08-16 | 2005-10-15 | Pfizer Prod Inc | Difluormethylen aromatische ether und ihre verwendung als inhibitoren des glycin-typ-1- transporters |
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GB0219153D0 (en) * | 2002-08-16 | 2002-09-25 | Pfizer Ltd | Substituted glycine derivatives for use as medicaments |
EP1587781A1 (en) * | 2002-11-05 | 2005-10-26 | Eli Lilly And Company | 3-aryloxy/thio-2,3-substituted propanamines and their use in inhibiting serotonin and norepinephrine reuptake |
WO2004096761A1 (en) | 2003-04-30 | 2004-11-11 | H. Lundbeck A/S | Aromatic oxyphenyl and aromatic sulfanylphenyl derivatives |
US20060223857A1 (en) * | 2003-08-21 | 2006-10-05 | Michael Didriksen | Combination of a serotonin reuptake inhibitor and a glycine transporter type 1 inhibitor for the treatment of depression |
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KR20060095865A (ko) * | 2003-10-14 | 2006-09-04 | 화이자 프로덕츠 인크. | 글리신 수송 억제제로서의 비시클릭 [3.1.0] 유도체 |
JP2007528879A (ja) * | 2004-03-12 | 2007-10-18 | ハー・ルンドベック・アクチエゼルスカベット | フェニルインダン誘導体 |
WO2005100301A1 (en) * | 2004-03-31 | 2005-10-27 | Eli Lilly And Company | 2-aryloxyethyl glycine derivatives and their use as glycine transport inhibitors |
TW200635587A (en) | 2004-12-01 | 2006-10-16 | Kalypsys Inc | Inducible nitric oxide synthase dimerization inhibitors |
UA95788C2 (xx) | 2005-12-15 | 2011-09-12 | Ф. Хоффманн-Ля Рош Аг | Конденсовані похідні піролу$кондесированные производные пиррола |
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MX2010010773A (es) | 2008-04-01 | 2011-04-11 | Abbott Gmbh & Co Kg | Tetrahidroisoquinolinas, composiciones farmaceuticas que las contienen y su uso en terapia. |
CN101613347B (zh) * | 2008-06-23 | 2012-07-04 | 中国人民解放军军事医学科学院毒物药物研究所 | 胺类化合物及其医药用途 |
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US9045459B2 (en) | 2010-08-13 | 2015-06-02 | AbbVie Deutschland GmbH & Co. KG | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9051280B2 (en) | 2010-08-13 | 2015-06-09 | AbbVie Deutschland GmbH & Co. KG | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
US8846743B2 (en) | 2010-08-13 | 2014-09-30 | Abbott Laboratories | Aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
US8877794B2 (en) | 2010-08-13 | 2014-11-04 | Abbott Laboratories | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
US8883839B2 (en) | 2010-08-13 | 2014-11-11 | Abbott Laboratories | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9309200B2 (en) | 2011-05-12 | 2016-04-12 | AbbVie Deutschland GmbH & Co. KG | Benzazepine derivatives, pharmaceutical compositions containing them, and their use in therapy |
TW201319049A (zh) | 2011-08-05 | 2013-05-16 | Abbott Gmbh & Co Kg | 胺基□唍、胺基硫□唍及胺基-1,2,3,4-四氫喹啉衍生物,包含彼等之醫藥組合物及彼等於治療之用途 |
EP2758403B1 (en) | 2011-09-21 | 2016-04-27 | Inception Orion, Inc. | Tricyclic compounds useful as neurogenic and neuroprotective agents |
CA2853254A1 (en) | 2011-11-18 | 2013-05-23 | Abbvie Inc. | N-substituted aminobenzocycloheptene, aminotetraline, aminoindane and phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9365512B2 (en) | 2012-02-13 | 2016-06-14 | AbbVie Deutschland GmbH & Co. KG | Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9656955B2 (en) | 2013-03-15 | 2017-05-23 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9650334B2 (en) | 2013-03-15 | 2017-05-16 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
AU2014336154A1 (en) | 2013-10-17 | 2016-04-28 | AbbVie Deutschland GmbH & Co. KG | Aminotetraline and aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
AU2014336153A1 (en) | 2013-10-17 | 2016-04-28 | AbbVie Deutschland GmbH & Co. KG | Aminochromane, aminothiochromane and amino-1,2,3,4-tetrahydroquinoline derivatives, pharmaceutical compositions containing them, and their use in therapy |
CN105384651B (zh) * | 2014-07-28 | 2017-03-22 | 昆明学院 | 含芳环的胺类化合物及其制备方法和应用 |
WO2019002173A1 (en) * | 2017-06-26 | 2019-01-03 | Esteve Pharmaceuticals, S.A. | COMPOUNDS HAVING MULTIMODAL ACTIVITY AGAINST PAIN |
WO2022187206A1 (en) * | 2021-03-01 | 2022-09-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Dual-target mu opioid and dopamine d3 receptors ligands; preparation and use thereof |
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DE3050800C2 (xx) * | 1979-03-22 | 1989-06-22 | Continental Pharma Inc., Bruessel/Bruxelles, Be | |
BE885303A (fr) * | 1980-09-19 | 1981-03-19 | Continental Pharma | Glycinamides |
JPH02129158A (ja) * | 1988-11-07 | 1990-05-17 | Nippon Steel Corp | 光学活性なグリシン誘導体及びその製造方法 |
ES2036926B1 (es) * | 1991-08-08 | 1994-01-16 | Uriach & Cia Sa J | "procedimiento para la obtencion de derivados de la (2-alquil-3-piridil)metilpiperazina". |
AU678503B2 (en) * | 1993-09-24 | 1997-05-29 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds and their use as squalene synthetase inhibitors |
DE4408528A1 (de) * | 1994-03-14 | 1995-09-28 | Hoechst Ag | Peptid-Oligonucleotid-Derivate, deren Herstellung und Verwendung |
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-
1998
- 1998-12-07 NO NO985711A patent/NO985711L/no unknown
Also Published As
Publication number | Publication date |
---|---|
EP1014966B1 (en) | 2006-08-02 |
WO1997045115A1 (en) | 1997-12-04 |
SK170098A3 (en) | 2000-02-14 |
HUP0100815A2 (hu) | 2001-08-28 |
IL127244A (en) | 2005-11-20 |
SK285854B6 (sk) | 2007-09-06 |
HUP0100815A3 (en) | 2002-11-28 |
EP1014966A1 (en) | 2000-07-05 |
JP4424450B2 (ja) | 2010-03-03 |
PT1014966E (pt) | 2006-12-29 |
CN1327383A (zh) | 2001-12-19 |
ES2270462T3 (es) | 2007-04-01 |
NO985711D0 (no) | 1998-12-07 |
DE69736441D1 (de) | 2006-09-14 |
BR9709501A (pt) | 2000-11-07 |
CA2254833C (en) | 2008-04-29 |
IL127244A0 (en) | 1999-09-22 |
AU3153097A (en) | 1998-01-05 |
EP1014966A4 (en) | 2001-10-04 |
NZ332780A (en) | 2000-07-28 |
CZ404298A3 (cs) | 1999-11-17 |
JP2002515037A (ja) | 2002-05-21 |
SI1014966T1 (sl) | 2006-10-31 |
CA2619901A1 (en) | 1997-12-04 |
NO985711L (no) | 1998-12-07 |
DK1014966T3 (da) | 2006-12-04 |
ATE334668T1 (de) | 2006-08-15 |
DE69736441T2 (de) | 2007-07-19 |
CA2254833A1 (en) | 1997-12-04 |
AU730789B2 (en) | 2001-03-15 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PD00 | Pending as of 2000-06-30 in czech republic | ||
MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20110529 |